The present research program is to increase our understanding of post-translational enzymatic methylation of protein, namely the modification of free carboxyl groups of proteins. The reaction is catalyzed by S-adenosylmethionine: protein-O-methyltransferase (EC. 2.1.1.24, protein methylase II) with S-adenosyl-L-methionine as the methyl donor. The enzyme system is complex involving protein enzyme, substrate, and a membrane bound specific natural inhibitor. The proposed work for the year will be: a) The purification of the enzyme and its inhibitor by an affinity chromatography, and comparative studies of the enzymes from mammalian and bacterial sources, specifically their catalytical and molecular properties. b) Investigation of the natural endogenous methyl acceptor proteins using a developing rat brain or testis. The measurement of the protein-methyl ester (the enzymatic product) and the identification of the site of esterification will be made. c) Enzymatic esterification of pituitary polypeptide hormone to investigate the structure and function relationship of the hormone.